The errors of vivisection part 1



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Part 1. Extracts from Science on Trial: The Human Cost of Animal Experiments, by Dr Robert Sharpe (Awareness, 1994)
Part 2 (Extracts from Betrayal of Trust, by Dr Vernon Coleman: European Medical Journal)

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Please note this article is in two parts. A menu to go on to Part 2 is in the above menu and at the end of this page.
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Part 1

FK506.
Animal experiments indicated that FK506, an anti-rejection drug, was too toxic for human use.[1][2] However, when used on human liver transplant patients, the results were found to be 'promising'.[3]

[1]R. Allison, Journal of the American Medical Association, 4 April 1990, p.1766.
[2]R. Y. Calne, et al, Lancet, 22 July 1989, p.227.
[3]J. Neuberger, Hepatology, vol. 13, pp.1259-1260.

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Radiation.
The Committee of Official Enquiry into the incidence of leukaemia in children near the Sellafield nuclear plant, declared the plant was not the cause; this decision was based on animal testing.[1] However, later research did support the view that the plant was responsible.[2]

[1]E. Millstone, in Animal Experiments: The Consensus Changes, ed. G. Langley (Macmillan, 1989).
[2]M. J. Gardner, et al, British Medical Journal, 17 February 1990, pp.423-429.

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Methysergide.
No life-threatening symptoms were observed when this drug, for migraine, was tested on animals[1], and the British Medical Journal acknowledged that it had not been possible to produce fibrotic lesions in laboratory animals[2]. And yet the British National Formulary (1993), found it necessary to warn that the drug should only be administered to humans by trained medical staff as it had been found that the drug had serious side-effects which arose from fibrous tissue (retroperitoneal fibrosis) and these included heart failure.

[1]R. Heywood in Animal Toxicity Studies: Their Relevance For Man, eds. C. E. Lumley and S. R. Walker (Quay Pub: 1990).
[2]K. A. Misch, British Medical Journal, May 18 1974, pp.365- 366.

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Suprofen/suprol.
This, an arthritis drug, was withdrawn globally in 1987 after reports of kidney problems and pain.[1] Those who reported these problems had to have their kidneys monitored for two years after they stopped using the drug.[2] And yet it was reported: 'In animal studies, Suprofen has been shown to have an excellent safety profile. No significant effects were observed on cardiac, renal [kidney] or central nervous system...in several species.[3]

[1]Drug Withdrawal from Sale, C. Spriet-Pourra and M. Auriche (PJB Publications, 1988).
[2]FDA Drug Review: Postapproval Risks, 1976-1985 (US General Accounting Office, April 1990).
[3]A. Yeardon, et al, Pharmacology, 1983, vol. 27, Suppl. 1, pp.87-94.

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Alcohol.
Until the twentieth century, alcohol was considered to be poisonous for the liver.[1] This view changed after experiments on animals,[1][2] and in 1934, animal testing concluded that there was no evidence for alcohol causing cirrhosis.[3][4]
Alcohol is of course today considered to be a liver toxin, but some still question this in view of the difficulty in inducing cirrhosis in laboratory animals.[5] In addition to this, alcohol appears to be more harmful to the circulatory system of human beings than animals. For example, excessive consumption raises the blood pressure in alcoholics, and yet this is not usually the case with rats.[6]
Furthermore, alcohol is able to damage the human heart but studies involving various animals who were given 'large amounts' of alcohol found that none suffered heart failure.[6]
Animal experiments also showed that Librium could assist in dealing with withdrawal although as some animals died, it also suggested there was a lethal side-effect.[7] In fact clinical tests carried out at an earlier time had already revealed that Librium was effective,[8] and it continues to be used in relation to alcohol withdrawal.

[1]H. J. Zimmerman, Alcoholism: Clinical and Experimental Research, 1986, vol. 10, pp.3-15.
[2]C. S. Lieber and L. M. DeCarli, Journal of Hepatology, 1991, vol. 12. pp.394-401.
[3]V. H. Moon, Archives of Pathology, 1934, vol. 18, pp.381- 424.
[4]As [2].
[5]R. F. Derr, et al, Journal of Hepatology, 1990, vol. 10, pp.381-386.
[6]J. V. Jones, et al, Journal of Hypertension, 1988, vol. 6, pp.419-422.
[7]D. B. Goldstein, Journal of Pharmacology and Experimental Therapeutics, 1972, vol. 183, pp.14-22.
[8]G. Sereny and H. Kalant, British Medical Journal, 9 January 1965, pp.92-97.

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Pesticides.
In 1986, the British Parliament's Agriculture Committee instigated a review into pesticides. Despite the general faith placed in animal experiments, the Committee was forced to concede that 'similar tests in different animal species often yield quite different results'.[1] One example was the organophosphate pesticide dipterex which caused nerve damage in human beings but not in animals.[2] One physician member of the National Poisons Unit advised the Committee that one documented case of human poisoning was worth 20,000 animal experiments.[1]
In view of the findings, the Committee declared: 'It cannot be satisfactory to rely on animals so much as a means of testing and, as other forms of testing becomes available, we recommend that they be adopted...we are satisfied from the evidence that we have received that animal testing can produce misleading results'.

[1]Special Report of the House of Commons Agriculture Committee, rep. FRAME News, 1987, No. 16, p.2.
[2]A. N. Worden, in Animals and Alternatives in Toxicity Testing, eds. M. Balls, et al (Academic Press, 1983).

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Arsenic.
For some seventy years, researchers were unable to connect arsenic with cancer due to being unable to verify the suspicion with animal experiments. Although arsenic had been connected with cancer as early as 1809, a report published in 1947 stated that the many animal experiments which had been conducted had only produced 'doubtful results'.[1]
Experiments continued after this date and even by 1969, researchers acknowledged that while it was believed there was a connection between cancer and arsenic, animal experiments had not offered any supporting evidence for this.[2] In 1977, a report yet again said that animal experiments had not produced supporting evidence of a link.[3] It was not until the end of the 1980s that researchers were finally able to produce the cancer in animals - nearly 200 years after the link had first been suggested.

[1]O.Neubauer, British Journal of Cancer, 1947, vol. 1, pp.192- 251.
[2]A. M. Lee and J. F. Fraumeni Jr., Journal of the National Cancer Institute, 1969, vol. 42, pp.1045-1052.
[3]F. W. Sunderman Jr., in Advances in Modern Technology, vol. 2, eds. R. A. Goyer and M. A. Mehlman (Wiley, 1977).

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Benzene.
As Benzene was widely used, e.g., for the manufacture of detergents, pharmaceuticals, etc., there was concern as there appeared to be a link with cancer. Animal experimentation did not support this view,[1] and some fourteen animal trials failed to show any connection between benzene and cancer.[2] Therefore workers were put at considerable risk in view of there being no 'evidence' of a link. It was not until the late 1980s, after dosing animals with benzene that cancer was induced.

[1]L. B. Lave, The American Statistician, 1982, vol. 36, pp.260-261.
[2]D. M. De Marini, et al, in Benchmarks: Alternative Methods in Toxicology, ed. M. A. Mehlman (Princeton Scientific Publishing, 1989).

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Lindane.
Lindane, while primarily known as an agricultural insecticide, it is also used in different forms, in a diluted amount, for lice and similar afflictions. However these can cause serious eye irritation,[1] and the British National Formulary 1993, warns that eye contact should be avoided. And yet in rabbits, when a far more concentrated solution was used, the effects were minimal. Additionally, exposure to lindane dust caused no problem to rabbits, but caused irritation to the eyes and respiratory systems of some people.[1]

[1]W. M. Grant, Toxicology of the Eye, 2nd edn (Charles Thomas, 1974).

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Dinitrophenol.
After considerable animal testing, this product was used as a treatment for obesity but after human usage it was noted that some patients were developing cataracts. Attempts were then made to replicate this in rats, rabbits, guinea pigs, and dogs, and yet none of the experiments produced any change to the lens of the eye.[1] A summary of the experimentation stated: 'All attempts to produce experimental cataracts in laboratory animals by various and repeated doses of dinitrophenol have been unsuccessful'.[2] It was only later that an experiment accidentally discovered that birds dosed with dinitrophenol developed cataracts.[1]
A similar situation arose with triparanol intended to reduce cholesterol levels. While the cataracts noticed in humans could be induced in rats and dogs (after very high doses) they could not be in rabbits and monkeys.[3] The product was withdrawn.

[1]B. H. Robbins, Journal of Pharmacology, 1944, vol. 80, pp.264-269.
[2]Rep. in ref [1].
[3]W. M. Grant, Toxicology of the Eye, 2nd edn (Charles Thomas, 1974).

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Chymotrypsin.
This product is used for ophthalmic surgery when dealing with cataracts. While recommended for human use,[1] it is harmful to a rabbit's eye, resulting in severe swelling of the cornea and sometimes causing perforation.[1]. It is stated: 'The rabbit cornea appears to differ significantly from the human cornea in its reaction to a-chymotrypsin'.[2]

[1]British National Formulary, No.26 (BMA and The Royal Pharmaceutical Society of G.B., 1993).
[2]Morton Grant, Toxicology of the Eye, (1974).

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Corticosteroids: Shock.
The idea for this medication arose after animal experiments when the survival rate of animals improved after being given the treatment just before, or after, shock.[1][2] Corticosteroids were then prescribed for people who required treatment for septic shock, which can often result in heart, respiratory and kidney failure.
However when The Drug and Therapeutic Bulletin analysed the trials it reported that: 'high-dose corticosteroids are ineffective for the prevention or treatment of shock associated with sepsis. They do not improve outcome, and make secondary infection worse. They may harm patients with impaired renal [kidney] function'.[1] In fact, one trial found that corticosteroids not only failed, but actually appeared to increase death among patients.[3]

[1]Drug and Therapeutics Bulletin, 1990, vol. 28, pp.74-75.
[2]S. G. Hershey, in Anaesthesiology, Proceedings of the VI World Congress of Anaesthesiology, Mexico City, April 1976, eds. E. Hulsz, et al (Excerpta Medica, 1977).
[3]R. C. Bone, et al. New England Journal of Medicine, 10 September 1987, pp.653-658.

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Acetylcholine.
This chemical (produced by nerve endings) was believed, after experiments with dogs, to dilate the coronary arteries. However when used with humans, it was found to narrow the blood vessels which can result in heart spasm.[1] Another body chemical, bradykinin, relaxes blood vessels in human brain tissue but contracts them in dogs.[2]

[1]S. Kalser, Journal of Physiology, 1985, vol. 358, pp.509-526.
[2]K. Schror and R. Verheggen, Trends in Pharmacological Sciences, 1988, vol. 9, pp.71-74.

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Leukotrienes (LT).
Those leukotrienes known as LTC4 and LTD4, constrict blood vessels in the skin of the guinea pig, but dilate corresponding issue originating from human beings and pigs.[1]

[1]P.J. Piper, et al, Annals of the New York Academy of Sciences, 1988, vol. 524, pp.133-141.

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Prostaglandins (PG).
These are a family of substances in human seminal fluid. In the heart tissue from cats and rabbits, PGE1 has no effect on contractile force or heart rate, and yet in rats, guinea pigs and chickens, it increases them.[1]
Because of such anomalies, some pharmacologists concede that the extrapolation from animals to humans is often invalid and acknowledge the increased interest in using tissue from human beings to overcome those restrictions which arise when using animal tissue.[2]

[1]S. Bergstrom, et al, Pharmacological Review, 1968, vol. 20, pp.1-48.
[2]Trends in Pharmacological Sciences, 1987, vol. 8, pp.289-290.

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Clonidine.
Animal experiments during the 1960s indicated that clonidine might be useful in treating migraine (Experiments with cats showed that the drug affected those processes believed to cause headaches). The drug was therefore introduced in 1969, but later research indicated that it was largely useless.[1].
However after being used as a nasal decongestant, it was discovered that clonidine could be effective when used to treat high blood pressure.[2]. However serious side-effects were then noted. Furthermore, attempts to replicate the condition in dogs and cats only provided inconsistent results,[3] and in the case of testing with rats, there were even more difficulties and disagreements.[4] The Drug and Therapeutic Bulletin therefore deems clonidine to be obsolete for the treatment of high blood pressure.[5]

[1]Drugs and Therapeutics Bulletin, 1990, vol. 28, pp.79-80.
[2]A. S. Niles in Clinical Pharmacology: Basic Principles in Therapeutics, 2nd edn, eds, K. L. Melmon and H. F. Morrelli (MacMillan, 1978).
[3]L. Hansson, et al, American Heart Journal, 1973, vol. 85, pp.605-610.
[4]M. J. M. C. Thoolen, et al, General Pharmacology, 1981, vol. 12, pp.303-308.
[5]Drug and Therapeutics Bulletin, 1984, vol. 22, pp.42-43.


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Isoprenaline.
During the 1960s, at least 3,500 young asthma sufferers died after using isoprenaline aerosol inhalers.[1] Fatalities occurred when the aerosol delivered 0.4mg of isoprenaline per spray.[2][3]
Attempts to replicate the same effects in laboratory animals were problematic and the New York Food and Drug Research Laboratory was forced to admit: 'Intensive toxicological studies with rats, guinea pigs, dogs and monkeys at dosage levels far in excess of current commercial metered dose vials...have not elicited similar adverse effects'.[4] It was only after artificially reducing the oxygen in the animals' tissue that vivisectors were able to increase the toxic effects of isoprenaline.[5]

[1]W. H. Inman, Monitoring for Drug Safety, ed. W. H. Inman (MTP Press, 1980).
[2]P. D. Stolley, American Review of Respiratory Diseases, 1972, vol. 105, pp.883-890.
[3]P. D. Stolley and R. Schimmar, Lancet, 27 October 1979, p.896.
[4]S. Carson, et al, Pharmacologist, 1971, vol. 18, p.272.
[5]British Medical Journal, 25 November 1972, pp.443-444.

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Phenacetin.
From the early 1950s, kidney damage associated with the prolonged use of combination painkillers was noted. Despite animal experiments, the reason for the damage could not be ascertained. It transpired that the animal experiments only served to further confuse the issue as while phenacetin was thought to be responsible, the damage could not be reproduced in the animals.[1] Furthermore, the experiments suggested it was the aspirin component that was causing the damage,[2] as aspirin, unlike phenacetin, readily induces kidney damage in laboratory animals.
It was only when human studies took place that it was realized that phenacetin was the cause,[3] leading to it being withdrawn in 1980 (when there was also the suspicion that it caused cancer).
An analysis concluded that if the research had only used animals the effects would not have been suspected or predicted.[1]

[1]I. Rosner, CRC Critical Reviews in Toxicology, 1976, vol. 4, pp.351-352.
[2]British Medical Journal, 17 October 1970, pp.125-126.
[3]K. G. Koutsaimanis and H. E. de Wardener, British Medical Journal, 17 October 1970, pp.131-134.

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Clioquinol.
During the 1960s there was an epidemic of drug-induced disease in Japan, related to clioquinol, the principal ingredient of Ciba- Geigy's antidiarrhoea drugs Enterovioform and Mexaform. It is believed that between 10,000 and 30,000 people fell victim to SMON (subacute myelo-optic neuropathy) which produced numbness, paralysis and eye problems including the loss of sight.[1] In 1970, the drug was banned in Japan, and fifteen years later, it was withdrawn globally.
Despite all the serious problems caused by the drug, those experiments carried out on animals, which included rats, cats, beagles and rabbits, revealed 'no evidence that clioquinol is neurotoxic'.[2]
Although there have been claims to have produced toxicity from clioquinol in mongrel dogs,[3] it has also been noted that different species yield different results, e.g., monkeys, hens, cocks and mice were only mildly affected even after they were given high doses while it was discovered that beagle dogs were 3-4 times less sensitive to clioquinol than mongrels.

[1]Lancet, 5 March 1977, p.534.
[2]R. Hess, et al, Lancet, 26 August 1972, pp.424-425.
[3]J. Tateishi, et al, Lancet, 10 June 1972, pp.1289-1290.

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Oral Contraception.
Studies of the pill have shown that of the side-effects which can occur, the most serious is that of problems with the circulatory system, i.e., blood clots, strokes and heart disease. By 1980 the CSM (Committee on Safety on Medicines) had received reports of over 400 deaths,[1] and further studies showed that some women using the pill had raised blood pressure. However none of these problems had been identified during animal experiments;[2] in fact the oral conceptive had produced the opposite effect (i.e., making it more difficult for the blood to clot) in some species.[3]
Prof. Briggs of Deakin University, Australia, noted: 'At multiples of the human dose no adverse effect on blood clotting was found in mice, rats, dogs, or non-human primates. Indeed, far from accelerating blood coagulation, high doses of oestrogens in rats and dogs prolonged clotting times. In sum, there is no appropriate animal model for the coagulation changes in women using oral contraceptives'.[4] In 1972 the CSM described how the tests which had been conducted on some 13,000 animals revealed that there was a connection between high doses of oral contraceptives and cancer.[5] And yet the rats and mice were so prone to cancer that even those who were not dosed with the oral contraceptive ('the control animals') developed high levels of disease; lung and liver tumours were found in 25% and 23% of the control mice, and adrenal, pituitary and breast tumours were found in 26%, 30% and 99% of the control rats.
In view of this, the British Medical Journal stated: 'It is difficult to see how experiments on strains of animals so exceedingly liable to develop tumours of these various kinds can throw any useful light on the carcinogenity of any compound for man'.[5]
Thus, it is those women who have used the pill who have really been the 'guinea pigs' for the drug.

[1]G. R. Venning, British Medical Journal, 22 January 1983, pp.289-292.
[2]R. Heywood, in Animal Toxicity Studies: Their Relevance for Man, eds, C. E. Lumley and S. R. Walker (Quay Publishing, 1990).
[3]R. Heywood and P. F. Wadsworth in Pharmacology of Estrogens, ed. R. R. Chaudhury (Pergamon Press, 1981).
[4]M. H. Briggs in Biomedical Research Involving Animals, eds. Z. Bankowski and N. Howard-Jones (CIOMS, 1984).
[5]British Medical Journal, 28 October 1972, p.190.

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Chloramphenicol.
Animal experiments indicated that chloramphenicol, an anti-biotic, was safe although it was equally clear that the drug produced side- effects in humans. Due to the serious side-effects, the drug was withdrawn in France.[1]
In 1952 American physicians discovered that chloramphenicol affected the nerve cells and they related how one patient had almost became blind and could only walk with great pain after taking chloramphenicol for just five months. This was only one of many reported cases when chloramphenicol produced optical and peripheral neuritis, and yet animal experimentation showed that the drug was virtually free of side-effects, even after prolonged use.[2]
A far more serious side-effect was the fact that chloramphenicol caused aplastic anaemia, an often fatal blood disease. Once again, animal experimentation did not provide any indication of this occurring and the British Medical Journal noted that chloramphenicol resulted in nothing worse than transient anaemia in dogs when injected for long periods: furthermore, no problems occurred when administered by mouth.[3]
It is now known that chloramphenicol is deadly by test-tube studies with human bone marrow cells.[4]

[1]C. Spriet-Pourra and M. Auriche, Drug Withdrawal From Sale, (PJB Publications, 1988).
[2]I. Wallenstein and J. Snyder, Annals of Internal Medicine 1952, vol. 26, pp.1526-1528.
[3]British Medical Journal, 19 July 1952, pp.136-138.
[4]G, M. I. Gyte and J. R. B. Williams, ATLA, 1985, vol. 13, pp.38-47.

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Halothane.
Halothane was introduced in 1956 and viewed as a considerable advance in anaesthesia. However it was soon found to be harmful to the liver and within five years there were over three hundred reported cases of 'halothane hepatitis'. The effects were sometimes fatal and nearly two hundred deaths in Britain were attributed to halothane.[1]
And yet animal experimentation had not provided any evidence of liver damage,[2] and despite many animal experiments and different 'animal models', the significance of their application to human beings was considered 'doubtful'.[3]
Even by 1986, when Britain's Committee on Safety of Medicine increased the warnings about liver toxicity,[4]. it was still unclear whether the same results could be induced in animals.[5]

[1]British Medical Journal, 5 April 1986, pp.949.
[2]Anaesthesiology, 1963, vol. 24, pp.1990-110.
[3]D. C. Ray and G. B. Drummond, British Journal of Anaesthesia, 1991, vol. 67, pp.84-99.
[4]Scrip, 2 October 1987, p.2.
[5]C. E. Blogg, British Medical Journal, 28 June 1986, pp.1691-1692.

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Butadiene.
This product was believed to produce cancer as cancer arose when it was tested on certain strains of laboratory mice, an animal widely used when seeking to assess the risk-element of chemical substances. When the dose was very high, cancer also arose in rats.
In view of the results of the animal experimentation, America's National Institute of Occupational Safety and Health (NIOSH) classified butadiene as a carciinogen.
And yet when humans who worked with butadiene were monitored, no extra cancer arose. In fact the number of deaths from cancer was less than the national average.[1] An editorial in Science therefore called for a review of the methodology which was used when considering the risk.

[1]P. H. Abelson, Science, 19 June 1992, p.1609.

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Pneumoconiosis.
Due to animal experimentation, it was believed that pneumoconiosis, a lung disease suffered by miners, was caused by silica rather than coal dust. Therefore mines, in which there was no exposure to silica, were viewed as being safe. Believing the problem was understood, there was no information about miners' pneumoconiosis until the early 1960s.[1]
As noted by the British Medical Journal, the idea that coal dust was safe arose from animal experimentation,[2] which not only absolved coal dust, but made silica the most likely culprit.[3] Nonetheless, the findings from the animal experimentation were shown to be suspect when miners, who only worked with pure coal dust or carbon, were found to have developed pneumoconiosis.[1][2] Thus it was shown that coal dust caused pneumoconiosis without any silica being present.
The results of the animal experimentation was further weakened when coal dust, collected from a mine where the incidence of pneumoconiosis was high, was found to be harmless to laboratory rats.[2] Naturally there is the question of how much serious illness was suffered by miners, and many deaths occurred, due to the incorrect information gleaned from animal experimentation.

[1]W. K. C. Morgan, in Occupational Lung Diseases, eds. W. K. C. Morgan and A. Seaton (Saunders, 1982).
[2]British Medical Journal, 17 January 1953, pp.144-146.
[3]I. U. Gardner, Journal of the American Medical Association, 19 November 1938, pp.1925-1936. Chronic Pulmonary Disease in South Wales III Experimental Studies, MRC special report series no. 250 (HMSO, 1945).

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Dermatitis.
Dermatitis, a skin condition, arises in many people when they come into contact with nickel compounds.[1] In fact nickel is considered to be the most common cause of dermatitis in women; in some cases it can result in severe eczema and disability.[2]
And yet in most animal testing, nickel is not found to be a skin sensitizer,[3] and, for example, the draize test on guinea pigs suggests that nickel does not produce an allergic reaction. Even in the two most widely used forms of animal testing, nickel produces no response (the Buehler test) or only a moderate response (the Maximization test).

[1]Medical Toxicology, eds. M J. Ellenhorn and D. G. Barceloux (Elsevier, 1988).
[2]Textbook of Dermatology, vol. 1, 5th edn, eds. R. H. Champion, et al (Blackwell Scientific Publications, 1992).
[3]P. A. Botham et al, Food and Chemical Toxicology, 1991, vol. 29, pp.275-286.

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Malaria.
Experiments using monkeys in malaria research led to the suggestion that coma in humans was caused by an increased amount of protein in the cerebro-spinal fluid, and this could be resolved by using steriods.[1] But in contrast to the animal experiments, it was ascertained that humans were not assisted by steroids when in a coma and if anything they were harmful.[2]
It was found that the time of coma was lengthened by some sixteen hours and serious complications, e.g., pneumonia, urinary tract infections, convulsions, etc., also occurred more often in those patients using steroids. Later research reported 'that the monkey model may simply not be relevant'.[1]

[1]Lancet, 2 May 1987, p.1016.
[2]D. A. Warrell, et al, New England Journal of Medicine, 11 February 1982, pp.313-319.

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Mianserin.
This drug, an antidepressant, can produce potentially fatal blood disorders and the British National Formulary recommends that people using the drug have full blood counts every 4 weeks in the first months of usage.[1] By 1988, the World Health Organisation had over 300 reports relating to white cell disorders.
Despite these problems, the animal experimentation which had been conducted had not predicted these effects,[2] although later test tube studies with human tissue did allow the effects to be observed.[3]

[1]British National Formulary, No. 26 (BMA and the Royal Pharmaceutical Society of GB, 1993).
[2]H. M. Clink, British Journal of Clinical Pharmacology, 1983, vol. 15, pp.2915-2935.
[3]P. Roberts, Drug Metabolism and Disposition, 1991, vol. 19, pp.841-843.

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Caged ball valve.
Dogs are preferred in cardiac experiments which include tests to develop an artificial mitral valve although these valves are known to produce fatal blood clots in the dogs.[1] Because of this, many surgeons have been deterred from carrying out human trials.[2]
To overcome the blood clots which occur, two experimental surgeons decided on a 'caged ball' valve,[3] as other devices proved fatal to those dogs on which they had been tested. Of the 7 dogs that received the caged ball valve, 6 died within 17 days and only one survived and this was for a few months. Despite this failure in dogs, the device was much more successful in clinical trials where blood clotting was not a problem.[4] The surgeons concluded: 'The marked propensity of the dog to thrombotic occlusion [blood clotting] ...from a mitral prosthesis is not shared by the human being'.[5]
The surgeons intended carrying out further experiments with their caged ball valve on animals but as it invariably resulted in the death of the animals, the surgeons had to produce a different valve made specially for use in the dogs. One would have thought this would have been sufficient to indicate animal experimentation was of no value in respect of human health, but they continued and found that while the different valve did not kill so many dogs so quickly, nearly 80% died in 46 days. The surgeons admitted that 'the species differences' forced them to design one type of valve for use in humans and another type for use in the laboratory animals.[5] Finally, the successful clinical use of another design of mitral valve replacement gave further proof that animal experimentation is of no use as none of the dogs used in the preclinical testing survived more than 40 hours.[6]

[1]A. V. Doumanian and F. H. Ellis, Journal of Thoracic and Cardiovascular Surgery, 1961, vol. 41, pp.683-695.
[2]G. H. A. Clowes, jr., Annals of Surgery, 1961, vol. 154, p.740.
[3]A. Starr, American College of Surgeons, Surgical Forum, 1960, vol. 11, pp.258-260.
[4]A. Starr and M. L. Edwards, Annals of Surgery, 1961, vol. 154, pp.726-740.
[5]A. Starr and M. L. Edwards, Journal of Thoracic and Cardiovascular Surgery, 1961, vol. 42, pp.673-682.
[6]N. S. Braunwald, et al, Journal of Thoracic and Cardiovascular Surgery, 1960, vol. 40, pp.1-11.

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Surgam.
This, an anti-inflammatory drug used for arthritis, was considered an improvement on other anti-inflammatory preparations as it did not damage the stomach, a major problem with this type of drug. It was advertised as providing 'gastric protection', being based on animal experimentation. However this claim could not be confirmed by clinical trials and as a consequence, Roussel, the manufacturer, was fined twenty thousand pounds for misleading advertising. The Lancet described how expert witnesses for both sides 'agreed that animal data could not safely be extrapolated to man'.[1]

[1]J. Collier and A. Herxheimer, Lancet, 10 January 1987, pp.113-114.

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Selacryn.
This diuretic product was tested on animals and no harmful effects were detected.[1] After being introduced in 1979, it had to be withdrawn in America the following year when over 300 cases of liver damage were reported, which included 24 deaths.[1] Development of the drug was cancelled in many countries including Britain.[2]

[1]S. Takagi, et al, Toxicology Letters, 1991, vol. 55, pp.287-293.
[2]C. Spriet-Pourra and M. Auriche, Drug Withdrawal From Sale (PJB Publications, 1988).

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Perhexiline.
This, a treatment for angina, was originally marketed in France in the 1970s. When it became linked to liver damage, it was withdrawn in Britain while other countries did not licence it at all. In fact some considered that it should never have been licensed.[1]
The animal experimentation conducted did not indicate the danger,[2] and even when high doses were administered to several different species for up to two years, there was no indication that the drug affected the liver.[3]
The company responsible for marketing perhexiline said: 'there has been an inordinate amount of animal work done...At this point we simply have been unable to induce hepatic [liver] damage in any species'.[4]

[1]D. G. McDevitt and A. M. MacConnachie, in Meyler's Side Effects of Drugs, 11th edn., ed. M. N. G. Dukes (Elsevier, 1988).
[2]C. T. Eason, et al, Regulatory Toxicology and Pharmacology, 1990, vol. 11, pp,288-307.
[3]J. W. Newberne, Postgraduate Medical Journal, 1973, vol. 49, April Suppl., pp.125-129.
[4]Ibid., p.130.

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Menthol.
Menthol is included in a number of cough and cold remedies, and is also used as an inhalent when conditions such as bronchitus and sinusitis arise. It is also used as a ointment. If it comes into contact with the eye it will produce burning sensation which can last up to thirty minutes although there are no after-effects. In stark contrast, menthol causes severe damage to the eye of the rabbit.[1]

[1]W. M. Grant, Toxicology of the Eye (Charles Thomas, 1974).

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Selenium disulphide (Selsun).
In view of this product being successful as an antidandruff shampoo, it was suggested that it might be of assistance for blepharitis, a painful and similar condition of the eyelids. Trials were then conducted in which a preparation with 0.5% selenium disulphide was applied to the lid margins. It was noted that if it came into contact with the conjunctivita there was irritation, and one patient developed conjunctivitis.[1] And yet animal experiments showed that: 'Selenium disulphide 0.5% ophthalmic ointment is nontoxic to rabbit corneas or conjunctivitas'.[2]

[1]G. C. Bahn, Southern Medical Journal, 1954, vol. 47, pp.749-752.
[2]J. W. Rosenthal and H. Adler, Southern Medical Journal, March 1962, p.318.

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Domestic and cosmetic products.
Researchers discovered that while coconut soap had a negligible effect on human skin, it causes skin irritation in rabbits. Pine oil cleaner also produced a 'moderate' reaction in rabbits and guinea pigs, whereas it only had a slight effect on human skin. Other substances have been found to have different effects on animals and humans, e,g., high and low carbonate detergents, phosphate detergents, enzyme detergents, sodium carbonate and lemon juice all had an insignificant effect on human skin while causing irritation in animals. Overall, only 6 of the 24 products tested on animals and humans had the same effect on humans, rabbits and guinea pigs. The report concluded: 'Neither the rabbit nor the guinea pig provides an accurate model for human skin. The skin responses of these animals differ in both degree and in kind from those found in human skin'.[1]
Similar findings arose with cosmetic ingredients. Researchers at the New Jersey Warner Lambert Research Institute observed that: 'Animal skin is entirely differently from human skin and that there may be no correlation between the mildness of a raw material on a rabbit's back and its safety during use on a human face'. They offer the example of isopropyl myristate which is deemed safe for human use but causes irritation in rabbits.[2]

[1]G. A. Nixon, et al, Toxicology and Applied Pharmacology, 1975, vol. 31, pp.481-490.
[2]M. M. Rieger and G. W. Battista, Journal of the Society of Cosmetic Chemists, 1964, vol. 15, pp.161-172.

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Domperidone.
This is used to treat nausea and vomiting, particularly those instances caused by anti-cancer treatment. The injectable form was withdrawn globally in 1986,[1] due to hazardous heart rhythm disturbances. However, this danger was not predicted by animal experimentation.[2] Dogs, the animal often used to test effects on the heart, were given 70 times the recommended human dosage, and yet no changes in the electrocardiogram occurred.[3]

[1]C. Spriet-Pourra and M. Auriche Drug Withdrawal From Sale (PJB Publications, 1988).
[2]R. Heywood, in Animal Toxicity Studies: Their Relevance For Man, eds. C. E. Lumley and S. R. Walker (Quay Publications, 1990).
[3]R. N. Brogden, et al, Drugs, 1982, vol. 24, pp.360-400.

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Squalene.
This is a natural constituent of human sebum, the substance formed by sebaceous glands surrounding the root of the hair; this keeps the skin lubricated and supple. It is extensively and safely used in cosmetics.[1] However, when used on the skin of rabbits and guinea pigs, it produces loss of hair, the very opposite of what occurs in human beings.[2]

[1]M. M. Rieger and G. W. Battista, Journal of the Society of Cosmetic Chemists, 1964, vol. 15, pp.161-172.
[2]B. Boughton, et al, Journal of Investigative Dermatology, 1955, vol. 24, pp.179-189.

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Prenylamine.
This product, a treatment for angina, was removed from the American market in 1988,[1] in view of it causing ventricular tachycardia, i.e., the heart beats abnormally fast and patients can faint. In stark contrast to this, animal experimentation revealed that prenylamine reduced the heart rate by up to 25% in cats, rabbits and guinea-pigs.[2]

[1]C. Spriet-Pourra and M. Auriche, Drug Withdrawal From Sale, (PJB Publications, 1988).
[2]H. Obianwu, Ata Pharmacology et Toxicology, 1967, vol. 25, pp.127-140.

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Furmethide.
Warnings had to be issued to ophthalmologists against the prolonged use of this product when treating glaucoma,[1] as it was noted that the tear passage became permanently obstructed in over 70% of those patients who used it for more than three months.
And yet those who conducted the animal experimentation related to this product (on rats, guinea pigs and rabbits) declared it 'entirely safe' and worthy of clinical trial.[2]

[1]R. N. Shaffer and W. L. Ridgway, American Journal of Opthalmology, 1951, vol. 34, pp.718-720.
[2]A. Myerson and W. Thau, Archives of Opthalmology, 1940, vol. 24, pp.758-760.

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Phenylbutazone (Butazolidine).
This was once widely used to treat arthritis, but was withdrawn in several countries and restricted in others, due to reports of aplastic anaemia (an often fatal blood disease caused by damage to the bone marrow) arising.[1]
Animal testing had indicated phenylbutazone to be a safe medication with no side effects even when ten times the dosage recommended for humans was administered to the animals.[2] The animal testing had certainly not suggested phenylbutazone would have a harmful effect on the bone marrow,[3] and a year after marketing, researchers said 'there have been no published reports of serious effects...on the hemopoietic [blood forming] system...in the experimental animal'.[4]
Noteworthy is the fact that later research involving test tube experiments using human bone marrow cell showed the dangers could be identified.[5]
It has been estimated that phenylbutazone and oxyphenbutazone (a closely related drug that has also caused aplastic anaemia which was withdrawn in 1985), have been responsible for 10,000 deaths worldwide.[6]

[1]C. Spriet-Pourra and M. Auriche, Drug Withdrawal From Sale, (PJB Publications, 1988).
[2]C. Hinz and I. M. Gaines, Journal of the American Medical Association, 1953, vol. 151, pp.38-39.
[3]R. Heywood in Animal Toxicity Studies: Their Relevance For Man, eds. C. E. Lumley and S. R. Walker (Quay Publishing, 1990).
[4]O. Steinbrocker, et al, Journal of the American Medical Association, 15 November 1952, pp.1087-1091.
[5]C. S. Smith, et al, Biochemical Pharmacology, 1977, vol. 26, pp.847-852.
[6]Estimate by Dr. Sidney Wolfe, in Lancet, 11 February 1984, p.353.

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Chloroform.
Deaths from chloroform were regularly reported in the second half of the nineteenth century; it was believed that it caused respiratory failure but this could be minimized by careful administration and monitoring. Regrettably animal experimentation supported the idea that chloroform affected respiration rather than the heart.[1]
Launder Brunton, in a communication to the Lancet,[2] summarized the results from the Second Commission: 'four hundred and ninety dogs, horses, goats, cats and rabbits used. Results most instructive. Danger from chloroform is asphyxia or overdose: none whatever heart direct'. With this confirmation, from animal experimentation, that chloroform did not stop the heart, anaesthetists continued to use chloroform.
In 1893, clinical observations completely contradicted the previous findings and showed that heart failure is the most common cause of death from chloroform.[1]

[1]K. B. Thomas, Proceedings of the Royal Society of Medicine, 1974, vol. 67, pp.723-730.
[2]Lancet, 7 December 1889, p.1183.

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Anaemia and iron.
When patients suffer iron deficiency, physicians prefer that they take iron by mouth, but if this is unsuccessful, iron is injected.[1] Due to animal experimentation, this option could have easily been discarded. Experiments which involved anaemia being induced in animals by iron deficiency or by repeated haemorrhage led the experimenters to conclude that injecting iron had no therapeutic value.[2] Fortunately, non-animal studies proved that human patients could be treated by iron injection.
Iron sorbitol is one type of injectable iron that could have been rejected for a different reason. Administration to rats and rabbits caused cancer at the injection site but once again non-animal trials showed that there was no hazard to human patients.[3]

[1]British National Formulary, no.276 (BMA and Royal Pharmaceutical Society of GB, 1993).
[2]G. N. Burger and L. J. Witts, Proceedings of the Royal Society of Medicine, 1934, vol. 27, pp.447-455.
[3]M. Weatherall, Nature, 1 April 1982, pp.387-390.

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Spinal injuries.
During the previous century, vivisectors attempted to develop an animal that would mimic spinal cord injuries (SCI) in humans.[1] One method used to achieve such injuries was dropping weights onto the spinal cord of cats.*** Through this, it was intended to devise therapies for SCI. Despite all the suffering experienced by laboratory animals, virtually no treatments were developed that work in human patients.[1]
In 1988, Dennis Maiman of the Dept. of Neurosurgery at the Medical College of Wisconsin, said: 'In the last two decades at least 22 agents have been found to be therapeutic in experimental SCI. Unfortunately, to date none of these have been proven effective in clinical SCI'.[1] In 1990 clinical trials showed that high doses of steroids could be beneficial. While this was subjected to animal testing, the fact remains that the testing was not only unnecessary but the animals gave inconsistent results, with some tests indicating the therapy would not work.[2]

[1]D. Maiman, Journal of the American Paraplegia Society, 1988, vol. 11, pp.23-25.
[2]S. R. Kaufman, Perspectives on Medical Research, 1990, vol. 2, pp.1-12.


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Psicofuranine.
When vivisectors tested psicofuranine for an anti-cancer treatment, the rats and mice used gave contradictory evidence.[1] The drug was effective against tumours in rats but had no effect on three different cancers in mice.
Physicians were also unable to properly assess the drug against human cancer as it caused severe side-effects in early human trials. It was found that the drug damaged the heart and yet no cardiac toxicity was found in the mice, rats, dogs or monkeys used in the testing.[1]
Although clinical study of psicofuranine was abandoned, animal experiments continued in an attempt to reproduce the heart ailments in humans. Yet again, no cardiac toxicity could be observed even when the animals (dogs and monkeys), were given up to 10 times the dose that would be harmful to humans.[1]

[1]C. G. Smith, et al, Journal of International Medical Research, 1973, vol. 1, pp.489-503.

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Sparsomycin.
During clinical trials, sparsomycin, an anti-cancer drug, was found to produce eye damage. And yet while sparsomycin was highly toxic in several animal species (as would be expected for an anti-cancer drug), no specific effect on the eye was found.[1]
After the eye damage was reported, vivisectors sought to induce the condition in rats and monkeys, but these attempts were unsuccessful even though the rats were dosed every day for two weeks with up to 300 times the amount that was found to harm humans.[1] No retinal toxicity was noted in additional animal tests and the drug was abandoned.

[1]C. G. Smith et al, Journal of International Medical Research, 1973, vol. 1, pp.489-503.

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Corticosteroids: the unborn.
Experimentation involving pregnant mice and rabbits indicate that corticosteroids are very dangerous to the unborn human child. In the case of mice, cortisone produces cleft palate in up to 100% of the offspring of some species.[1] And in the case of rabbits, corticosteroids affect the heart and they can also cause severe growth retardation in the uterus, and death of the foetus. In stark contrast, rats and monkeys are very tolerant to corticosteroids in pregnancy.[2]
Researchers have noted the 'very wide species variation',[2] and despite the results of animal testing, cortisone is not considered harmful to human babies.[1]

[1]R. M. Ward and T. P. Green, Pharmacology and Therapeutics, 1988, vol. 36, pp.326.
[2]R. K. Sidhu in Drugs and Pregnancy: Human Teratogenesis and Related Problems, ed. D. F. Hawkins (Churchill Livingstone, 1983).

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Iproniazid.
This was originally manufactured for the treatment of tuberculosis, but was subsequently used as an anti-depressant. Although it was considered 'harmless' on the basis of animal tests,[1] iproniazid produced fatal cases of liver damage in humans, and the drug was eventually abandoned.[2]

[1]J. Boyer in Clinical Pharmacology: Basic Principles in Therapeutics, 2nd edn., eds. K. I. Melmon and H. F. Morrelli (Macmillan, 1978).

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Thalidomide.
This was first introduced as a sedative by the German drug company Chemie Grünenthal in 1957, and by the Distillers company in Britain a year later. Although animals could tolerate massive doses without ill-effect,[1] thalidomide was soon found to cause peripheral neuritis in human patients.
William McBride, an Australian obstetrician, was alerted to thalidomide's most notorious side-effect after seeing three babies born with very unusual birth defects. Regrettably, his warnings to the medical profession were delayed because he attempted to confirm his suspicions by experiments on mice and guinea pigs, both of which were resistant to the drug.[2] It was only after he saw more human cases, did McBride publish his findings.
Although it was not specifically tested for birth defects before it was marketed, subsequent experiments revealed 'extreme variability in species' susceptibility to thalidomide'.[3] For example, mice could safely tolerate eight thousand times the dose which was found harmful to human babies.[4]
In his book, Drugs as Teratogens, Schardein writes: 'In approximately ten strains of rats, fiftee
n strains of mice, eleven breeds of rabbits, two breeds of dogs, three strains of hamsters, eight species of primates, and in other such varied species as cats, armadillos, guinea pigs, swine and ferrets, in which thalidomide had been tested, teratogenic effects [birth defects] have been induced only occasionally'.
Scientists eventually found that birth defects similar to those occurring in humans could be induced in certain types of rabbit and primate. Nonetheless, New Zealand white rabbits had to be dosed with three hundred times the amount that was dangerous to humans.[5]
The thalidomide tragedy prompted additional extensive testing of drugs and chemicals in pregnant animals, but some scientists believe that: 'Animal malformations seldom correlate with those of humans'.[6] Additionally, 'No animal model has been found which responds satisfactorily to all known teratologic agents in humans to permit reliable screening of substances for their teratologic potential. Careful surveillance, reporting and prospective study...remain the mainstays for detection of adverse effects following foetal drug exposure'.[6]

[1]R. D. Mann, Modern Drug Use, an Enquiry on Historical Principles (MTP Press, 1984).
[2]The Sunday Times 'Insight' Team: Suffer the Children: the Story of Thalidomide, (Andre Deutsche, 1979).
[3]T. H. Shepard, Catalogue of Teratogenic Agents (John Hopkins Press, 1976).
[4]S. K. Keller and M. L. Smith, Teratogenesis, Carcinogenesis and Mutagenesis, 1982, vol. 2, pp.361-374.
[5]New Zealand White rabbits were sensitive to doses of 150mg/Kg of thalidomide (ref. 6), while the dangerous human dose was 0.5mg/Kg (ref. 4).
[6]R. M. Ward and T. P. Green, Pharmacology and Therapeutics, 1988, vol. 36, p.326.


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Mitoxantrone.
This drug was produced for the treatment of cancer without side- effects on the heart. After beagles, on whom the drug was tested , 'failed to demonstrate cardiac failure',[1] researchers believed that it was safe. However in clinical trials, a number of patients suffered side-effects including heart failure; more widespread use of the drug confirmed that cardiac toxicity was a major problem with the drug.
Data from over three thousand patients who were given the drug included nearly a hundred reports of cardiac side-effect with twenty- nine of heart failure.[2] A recent study indicated that 20% of patients develop cardiotoxicity after using mitoxantrone.[3]

[1]R. Stuart Harris, et al, Lancet. 28 July 1984, pp.219- 220.
[2]Martindale: The Extra Pharmacopoeia, 29th edn., ed. J. E. F. Reynolds (Pharmaceutical Press, 1989).
[3]A. Stanley and G. Blackledge, Side Effects of Drugs, Annual 15, eds. M. N. G. Dukes and J. K. Aronson (Elsevier, 1991).

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Carbenoxalone.
This was introduced during the 1960s for the treatment of peptic ulcers. Before being marketed it was tested on animals and the tests indicated that carbenoxalone was safe and there were no harmful effects.[1] When vivisectors realized that humans metabolized carbenoxalone differently to rats, mice and rabbits, further experiments were carried out on monkeys, but yet again, there was no evidence of toxicity.[1]
When carbenoxalone began to be used by human patients, salt and water retention occurred and this led to high blood pressure, swelling, weight gain, muscle weakness and heart failure. The British National Formulary advises other drugs are preferred and if carbenoxalone is used, treatment must be carefully monitored.[2]

[1]C. T. Eason, et al, Regulatory Toxicology and Pharmacology, 1990, vol. 11, pp.288-307.
[2]British National Formulary, no.26 (BMA and the Royal Pharmaceutical Society of G.B., 1993).

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Clindamycin.
After the antibiotic clindamycin was given to rats and dogs every day for a year, it was found that the animals could tolerate twelve times the recommended human dose.[1]
However, Britain's Committee on the Safety of Medicines was forced to warn the medical profession about the dangers of clindamycin, one of which was the sometimes-fatal intestinal disease, pseudomembraneous colitis. By 1980, 36 deaths had been reported.[2] Although the problem can occur with other antibiotics, it is more frequently seen with clindamycin and the British National Formulary warns that patients should stop using clindamycin immediately if side-effects develop.

[1]The British National Formulary (No. 26, 1993) says the maximum oral dose for severe infections is 450mg every six hours, i.e., 25mg/kg for a person weighing 70 kg taking 4 doses in 24 hours. Rats and dogs could tolerate more than 300mg/kg (J. E. Gray, et al, Toxicology and Applied Pharmacology, 1972, vol. 21, pp.516- 531).
[2]G. R. Venning, British Medical Journal, 15 January 1983, pp.199-202.

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Leukaemia treatment.
For decades, in an attempt to find a treatment for leukemia, tens of thousands of chemicals have been used in mice which have been given leukaemia. This has proved highly ineffective. One scientist has estimated that for every 30-40 drugs that are effective in treating mice with cancer, only one will work with humans.[1]. During the 1980s, researchers admitted that the American NCI (National Cancer Institute) was failing to identify promising new treatments.[2][3]
A new strategy involves test tube studies rather than mice, at least for the preliminary experiments. Drugs that appear to be promising are then tested on animals so the prospect of misleading results is still very much there.[4]

[1]D. D. Von Hoff, Journal of the American Medical Association, 10 August 1979, p.503.
[2]R. Kolberg, Journal of NIH Research, 1990, vol. 2, pp.82- 84.
[3]A. Pihl, International Journal of Cancer, 1986, vol. 37, pp.1-5.
[4]S. E. Salmon, Cloning of Human Tumor Stem Cells (Alan Liss, 1980).

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Pronethalol and Propranolol.
The first agents used as beta-blockers, for the treatment of heart conditions, were pronethalol and propranolol. While pronethalol was found to be safe and effective with laboratory animals, but failed the clinical tests, propranolol appeared to be toxic in numerous animal experiments, and yet it is widely used in clinical practice, i.e., treating humans.
Pronethalol was 'well tolerated' by rats and dogs in prolonged toxicity tests at high doses except for occasional effects on the central nervous system.[1] In complete contrast, clinical trials revealed an unacceptable number of side-effects,[2] including heart failure - a hazard not predicted by the animal experiments which had been conducted.[1] Shortly after, long-term tests in a particular strain of laboratory mouse produced cancer of the thymous gland but no carcinogenic effects were ever found in rats, guinea pigs, dogs, monkeys or other types of mouse.[1]
Pronethalol was promptly replaced by propranolol but tests in rats, dogs and mice resulted in further development being jeopardized.[3] Moderate to high doses caused rats to collapse and dogs to vomit severely.[1] Deaths also occurred in mice shortly after dosing. When the amount of the drug was reduced to the dosage that would be used by humans, propranolol was said to be 'well tolerated', although even then, some of the rats still had heart lesions.[1]

[1]M. Cruickshank, et al, Safety Testing of New Drugs, eds. D. R. Lawrence, et al (Academic Press, 1984).
[2]W. Sneader, Drug Discovery: The Evolution of Modern Medicine (Wiley, 1985).
[3]D. R, Laurence, et al, eds., Safety Testing of New Drugs (Academic Press, 1984).

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Librium and Valium.
These were the first of a new type of tranquillizing drug which appeared in the 1960s. Soon after their introduction, the medical profession became aware of cases of dependence although it was nevertheless believed that high doses were necessary.[1] At the usual therapeutic doses, dependence was thought to be uncommon and not a serious problem and this idea prevailed for some twenty years as laboratory research confirmed it: 'animal experiments...do not indicate the potential for the development in the human of dependence at therapeutic dosage levels'.[2]
At the same time it is also known that 'animal studies...do not predict clinical dependence potential reliability',[3] and careful human observations revealed that tranquillizers could in fact induce dependence at ordinary doses. By the mid-1980s, some 500,000 people in Britain alone were addicted to this treatment.[4]

[1]H. Peturrson and M. Lader, Dependence on Tranquillizers (OUP, 1984).
[2]J. Marks, The Benzodiazepines (MTP Press, 1978).
[3]Drug and Therapeutics Bulletin, 1989, vol. 27,28.
[4]The Benzodiazepines in Current Clinical Practice, eds., H. Freeman and Y. Rue (Royal Society of Medicine Services, 1987).

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Rifampicin.
In the early 1970s, doctors became aware of women who, while using 'the pill', became pregnant.[1] Of 88 women who used oral contraceptives in addition to the antituberculous drug rifampicin, 75% suffered disturbances to their menstrual cycle and 5 became pregnant. The British National Formulary (1993) advised doctors who prescribed rifampicin to recommend to patients that they use additional means of contraception.
It was discovered that rifampicin accelerates the breakdown of other medicines,[2] and in these cases it had stimulated the patient's liver to metabolize/breakdown the pill. Another example was methadone where rifampicin led to withdrawal symptoms by reducing the amount of the drug. In one case, a patient rejected a kidney graft because rifampicin reduced the dose of the immunosuppresive drug which had been given.
Rifampicin's peculiar effects had not been predicted by animal experimentation.[3] After the discovery of the effects in humans, further animal experimentation was conducted but this proved contradictory. For example. the drug's action could not be reproduced in rats.[4] In mice however, prolonged treatment with rifampicin did stimulate the liver's metabolic processes; however a single dose had the opposite effect of slowing down metabolism.[4] If rifampicin had been tested on human liver tissue rather than on live animals, it is likely the problems would have been predicted.[5]

[1]Reported in J. P. Mumford, British Medical Journal, 11 May 1974, pp.333-334.
[2]H. Meyer, et al, in Meyer's Side Effect of Drugs, 11th edn., ed. M. N. G. Dukes (Elsevier, 1988).
[3]E. Nieschlag, Pharmacology and Therapeutics, 1979, vol. 5, pp.407-409.
[4]D. Pessayre and P. Mazel, Biochemical Pharmacology, 1976, vol. 25, pp.943-949.
[5]A. M. Jezequel, et al, Gut, 1971, vol. 12, pp.984-987.

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Taxoxifen.
This was developed during the 1960s as an oral contraceptive. However, while it prevented ovulation and terminated pregnancy in rats,[1] it stimulated ovulation in women and became listed as a treatment for infertility.[2]
It is used also in breast cancer therapy as it blocks the action of oestrogen in breast tissue. In monkeys, and rats at low doses, it also acts as an anti-oestrogen, but in mice, dogs, and rats at high doses, it has the opposite effect, behaving like an oestrogen.[1] Due to the different results of animal experimentation, it was admitted that 'significant species variation has been observed in target tissue response to oestrogens and anti-oestrogens making it hazardous to predict therapeutic activity in the human by extrapolation of effects in experimental animals'.[3]
Other conflicting results from animal testing has occurred, e.g., taxoxifen produces liver tumours in rats but not in mice,[4] and does not appear to do so in humans. Due to the conflicting results the two leading British cancer charities disagreed over taxoxifen and the Medical Research Council withdrew its support and decided to initiate new tests. The Imperial Cancer Research fund said: 'We are going to be in a position where the animal rights people are going to be saying to us: 'you ignore animal data when you choose to'.'[5]
Yet further doubts arose through a subsequent study which suggested an increased risk of womb cancer among the breast cancer patients being tested with the drug. However overall, the drug is said to have few side-effects and according to the manufacturer, the main reason to stop taking the drug is if nausea and vomiting begin.[1] This comes as a surprise as it had been noted: 'None of the toxicological studies produced any evidence of vomiting even though high doses were used in dogs which we consider to be a predictive species for vomiting in man.[1].

[1]M. J. Tucker, Safety Testing of New Drugs, eds. D. R. Laurence, et al (Academic Press, 1984).
[2]British National Formulary, No. 26 (BMA and the Royal Pharmaceutical Company of GB, 1993).
[3]P. K. Devi, in Pharmacology of Estrogens, ed. R. R. Chaudhury (Pergamon Press, 1981).
[4]I. N. White, et al, Biochemical Pharmacology, 1993, vol. 45, pp.21-30.
[5]P. Brown, New Scientist, 21 March 1992, p.9.

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Steroids.
Corticosteroid drugs are widely used in medicine although they have many side-effects. It is admitted that there are 'remarkable differences in susceptibility to glucocorticosteroids between various species' with animals classified as steroid-resistant or steroid-sensitive.[1]
In mice, a single dose of cortisone produces a 90% decrease in the thymus (an organ that plays a crucial role in immunity). In contrast, the same dose of cortisone given to a guinea-pig every day for a week, only produces a 37% decrease. Furthermore, the same effect is difficult to achieve in other species.[1]
Much of the research on corticosteroids have been carried out on steroid-sensitive animals (e.g., mice, rats, rabbits, and hamsters) whereas human beings fall into the steroid-resistant category.[1] Researchers at the University of Dundee acknowledged: 'the mode of action of these drugs is very complicated, so it is regrettable that most of the extensive literature on animal experimental work is irrelevant to human therapeutics since many species respond in a very different manner from man'.[2]

[1]H. N. Claman, New England Journal of Medicine, 24 August 1972, pp.388-397.
[2]J. S. Beck and M. C. K. Browning, Journal of the Royal Society of Medicine, 1983, vol. 76, pp.473-479.

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X-rays.
In 1956, the British medical profession drew attention to a link between X-rays during pregnancy and subsequent childhood cancers.[1] Within a short time, similar findings were reported in respect of American children. And yet for a quarter of a century, scientists doubted that X-rays could cause such cancer and cited animal experimentation to argue that the foetus is not particularly sensitive to radiation.[2]
In fact, compared with other species, the human foetus is more susceptible to the carcinogenic effects of X-rays,[2] and this was confirmed during the 1980s.[3]

[1]A. M. Stewart, et al, Lancet, 1 September 1956. p.447; British Medical Journal, 28 June 1958, pp.1495-1508.
[2]E. B. Harvey, et al, New England Journal of Medicine, 28 February 1985, pp.541-545.
[3]E. G. Knox, et al, Journal of the Society of Radiological Protection, 1987, vol 7, pp.3-15; E. A. Gilman, et al, Journal of the Society of Radiological Protection, 1988, vol. 8, p.308.

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Methanol.
This is used in a wide range of consumer products, e.g., solid fuel, antifreeze, paint remover and varnishes. It is also consumed as a heap alternative to alcohol.
Although methanol is a highly poisonous, potentially lethal substance, this was not realized for some years.[1] Laboratory animals such as rats and mice are resistant to its effects,[2] and animal experiments in the early part of the twentieth century gave the impression that methanol was only marginally toxic, and far less poisonous than alcohol.[3]
In reality, methanol is ten times more toxic; a single dose of methanol can result in temporary or permanent blindness in human beings.[4] However, this does not occur in rats, mice, dogs, cats, rabbits or chickens.[3] It was only in the 1960s and again in the next decade that the actual symptoms of methanol poisoning were induced in monkeys.[2]
As is obvious from the above, animal experimentation was both highly misleading and dangerous. Some good treatment results were obtained in the earlier part of the twentieth century by using bicarbonate to treat human poisoning, but the results were undermined by animal experimentation. In 1955 an analysis stated: 'It is indeed deplorable that about thirty years before the good effects of this treatment became commonly known...it seems that the authors of medical textbooks have paid more attention to the results of animal experimentation than to clinical observations'.[3] The treatment not only failed in animals but actually proved fatal, prompting some researchers to advise against using it.
Another method involves administering alcohol to reduce the toxicity of methanol. While this is effective in human beings, animal tests suggested that this practice would increase the danger of methanol. Once again, animal experimentation discouraged using this method of treating human poisoning.[3]

[1]M. J. Ellenhorn and D. G. Barceloux, Medical Toxicology: Diagnosis and Treatment of Human Poisoning (Elsevier, 1988).
[2]T. R. Tephly, Life Sciences, 1991, vol. 48, pp.1031- 1041.
[3]O. Roe, Pharmacological Reviews, 1955, vol. 7, pp.399- 412.
[4]P. Wingate, Medical Encyclopedia, (Penguin, 1983).

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Aminorex.
During the 1960s, physicians in Switzerland became aware of a sudden rise in obstructive pulmonary hypertension, a dangerous lung disease. The cause was traced to the drug aminorex which had been used for treating obesity.[1] The drug was found to cause chest pains, difficulty in breathing, fainting, heart problems and in some cases, death.[2] The deadly side-effects of this drug had not been predicted by the animal experimentation which had been conducted.[3]. In view of its dangers, the drug was withdrawn in 1968.
Animal experimentation continued after withdrawal and even then, long administration to rats failed to induce the disease.[2] In dogs, the drug increased lung pressure,[1] but its relevance to the human condition is unclear since later analysis concluded that: 'pulmonary hypertension cannot by induced in experimental animals even with aminorex'.[4]

[1]F. Follath, et al, British Medical Journal, 30 January 1971, pp.265-266.
[2]E. H. Ellinwood and W. J. K. Rockwell in Meyler's Side Effects of Drugs, 11th edn, ed. M. N. G. Dukes (Elsevier, 1988).
[3]A. D. Dayan in Risk-Benefit Analysis in Drug Research, ed. J. F. Cavalla (MTP Press, 1981).
[4]P. H. Connell in Side Effects of Drugs Annual - 3, ed. M. N. G. Dukes (Excerpta Medica, 1979).

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Diethylstilbestrol (DES).
On the basis of what animal experimentation revealed, the synthetic oestrogen Diethylstilbestrol (DES) was suggested as a means by which miscarriage could be avoided.[1] Although no proper clinical, i.e., human, trials were conducted,[2] the procedure became widely accepted and to 1971, up to 3 million pregnant women in America alone were given DES.
However, DES was found to be ineffective; in 1953 trials had shown that DES did not work,[3] although this study failed to report that DES increased abortion, neonatal deaths and premature deaths, a conclusion that could have been made from the available data.[4]
Thus, DES was not only ineffective, it was dangerous and in 1971, researchers discovered how dangerous it was when they traced a link between exposure to DES and a previously rare form of vaginal and cervical cancer in the daughters of those women who had taken the drug while pregnant.[5] Nearly six hundred cases were reported,[6] and DES proved to be a biological time-bomb as its side-effects continued to appear in the sons and daughters of women who took the drug.
Although, in 1938, it was found that DES caused breast cancer in male mice, this information was of no value as the cancer-causing potential of other oestrogens varied according to the strain of mouse used.[7] Furthermore, the consensus among vivisectors at the time was that oestrogens did not produce cancer,[7] rather they gave male mice mammary glands and therefore made them susceptible to the same cancer-causing factors that arose in female animals. In fact, a summary of the animal data found 'only meagre evidence' that oestrogens caused cancer of the cervix.[7]
It was not until the 1970s that it became clear that in contrast to the majority of animal experiments, DES was a potent cause of cervical cancer in women.

[1]Health Action International, 'Problem Drugs' pack, 13 May 1986.
[2]D. Brahams, Lancet, 15 October 1988, p.916.
[3]W. J. Dieckmann, et al, American Journal of Obstetrics and Gynaecology, 1953, vol. 66, pp.1062-1081.
[4]Y. Brackbill and H. W. Berendes, Lancet, 2 September 1978, p.520.
[5]A. L. Herbst, et al, New England Journal of Medicine, 22 April 1971, pp.878-881.
[6]C. Vanchieri, Journal of the National Cancer Institute, 1992, vol. 84, pp.565-566.
[7]S. Peller, Cancer in Man (Macmillan, 1952).

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Pethidine.
On the basis of experiments with dogs, the narcotic analgesic pethidine was considered to be non-addictive.[1] This error was not realized because in dogs, the drug was metabolized (broken down) much more quickly, resulting in less exposure to the drug. In fact, dogs metabolize pethidine six times faster than humans.[2]
Such differences in metabolism are the rule rather than the exception;[2,3] a former director of Wellcome Research Laboratories admitted that 'every species has its own metabolic pattern, and no two species are likely to metabolize a drug identically'.[4]

[1]B. Brodie, Pharmacologist, 1964, vol. 6, pp.12- 26.
[2]R. Levine, Pharmacology, Drug Actions and Reactions (Little, Brown and Co, 1978).
[3]G. Zbinden, Advances in Pharmacology, 1963, vol. 2, pp.1-112.
[4]M. Weatherall, Nature, 1 April 1982, pp.387-390.

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Digoxin and Digitoxin.
These heart drugs are pure substances extracted from digitalis, the value of which in treating heart failure and cardiac arrhythmias originated from the studies of human patients;[1,2] (despite its value, care must be taken over high doses which can be toxic). Fortunately the drugs did not derive from animal experiments as the doses which were considered safe for rats, guinea-pigs, dogs and cats can in fact kill human beings.[3] Digoxin's lethal dose is now more accurately determined by test-tube studies using human cells.[4]
Animal experimentation also indicated that digitalis raised the blood pressure and as a result of this, the drug was widely considered to be dangerous for certain patients and should not be prescribed to them. Fortunately, studies, not using animals, showed this to be false and digitalis can be, and is used for the treatment of human patients with great benefit.[2]

[1]W. Sneader, Drug Discovery: The Evolution of Modern Medicine (Wiley, 1985).
[2]T. Lewis, Clinical Science (Shaw and Sons Ltd, 1934).
[3]G. T. Okita, Federation Proceedings, 1967, vol. 26, pp.1125-1130.
[4]R. Jover, et al, Toxicology In Vitro, 1992, vol. 6, pp.47-52.

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Detergents.
Detergents are not only used in domestic and industrial settings, i.e., experimentation which sought to increase the penetration of therapeutic drugs across the cornea used a number of dilute detergents which were assessed in the eyes of human volunteers. Although these were deemed 'generally harmless to rabbit eyes', some caused pain and irritation in the human volunteers.
For example, Brij 58 resulted in 'alarming' changes to the surface of the human eye, accompanied by discomfort and impaired vision.[1] And yet in rabbits, Brij 58 is designated a 'non-irritant'.[2]
A 3% solution of a similar product called Brij 35 produced delayed irritation in volunteers but was once again non- irritating to the rabbit eye, and this was even when undiluted.[1] Another detergent, dupanol, caused immediate severe pain in human subjects,[1] but was deemed to only have moderate effects in the eyes of rabbits.[3]

[1]R. J. Marsh and D. M. Maurice, Experimental Eye Research, 1971, vol. 11, pp.43-48.
[2]M. Cornelis, et al, ATLA, 1991, vol. 19, pp.324- 326.
[3L.W. Hazelton, Proceedings of the Scientific Section of the T.G.A, 1952, vol. 17, pp.509.

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Cancer treatment.
Many cancer patients suffered unnecessarily when it was believed that large doses of anticancer drugs were necessary for efficient treatment. It was held that to reduce the tumour size, chemotherapy also had to be toxic.[1]
This idea was based on animal experimentation,[1,2] even though there were early warning signs that patients survived longer when treated with comparatively non-toxic doses, despite the drug having a smaller effect on the tumour size.[3]
Studies in the 1960s concluded that toxicity was not necessary and could be counterproductive.[2] In 1976, cancer specialists in London found that the data from animal experimentation, on which the high dose concept was based, are not necessarily valid for human patients,[1] and argued that 'alternative methods of improving the selectivity of cancer chemotherapy must be explored'.

[1]M. H. N.Tattersall and J. S. Tobias, Lancet, 13 November 1976, pp.1073-1074.
[2]I. D. Bross, Perspectives on Animal Research, 1989, vol. 1, pp.83-108.
[3]M. A. Schneiderman and M. J. Krant, Cancer, Chemotherapy Reports, 1966, vol. 50, pp.107-112.

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AIDS.
The fact that even chimpanzees do not develop AIDS when infected with HIV naturally casts doubts on whether animal experimentation concerned with AIDS can have any possible value.[1] Some AIDS researchers appear to have grasped this fact as vaccines which failed to protect chimpanzees from HIV were nevertheless tried in human trials.[2]
Animal experimentation has the potential to be dangerous as the failure to induce AIDS in laboratory animals has led some to argue that HIV is not the cause of AIDS.[3]
There is a further danger by producing an 'animal model' of AIDS as this may simply produce an animal version of AIDS and could also promote hazardous changes in the manner in which AIDS is spread.

[1]P. Newmark, Nature, 19 October 1989, pp.566-567.
[2]A. S. Fauci and P. J. Fischinger, Public Health Reports, 1988, vol. 103, pp.203-236.
[3]New Scientist, 3 March 1988, p.34.
[4]J. Marx, Science, 16 February 1990, p.809. P. Lusso, et al, Science, 16 February 1990, pp.848-852.

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Furosemide.
Furosemide is successfully used for the treatment of cardiovascular and kidney disease in human beings. However, in mice it causes massive liver damage and similar effects have been found in rats and hamsters.[1] And yet liver toxicity is not a major problem for human patients.[2] The harmful effects in mice have been traced to a breakdown product of furosemide which is not found to any serious extent in the human body.[3] Fortunately the adverse effects in mice were reported after the safety in people had been established.[3] If it had been otherwise, the drug may have never been introduced.
A comparison of human and animal test data shows that the case of furosemide is not an isolated instance. At most, only one out of every four side-effects produced by animal tests actually occurs in human beings.[4] Consequently animal testing leads to the rejection of medicines which are potentially valuable for treating human illnesses.

[1]R. M. Walker and T. F. McElligott Journal of Pathology, 1981, vol. 135, pp.301-314.
[2]M. N. G. Dukes in Meyler's Side Effects of Drugs, 11th edition, ed. M. N. G. Dukes (Elsevier, 1988).
[3]M. Weatherall, Nature, 1 April 1982, pp.387-390.
[4]A. P. Fletcher, Journal of the Royal Society of Medicine, 1978, vol. 71, pp.693-698.

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Cyclosporin.
This is used to prevent the rejection of transplanted organs: while hailed as a major advance over existing drugs, side- effects are common and sometimes dangerous. The most serious hazard is kidney damage,[1] an effect that was not predicted by the initial animal experimentation.[2] And yet kidney toxicity has been reported in almost 80% of kidney transplant patients receiving the drug.[2] Some heart transplant patients who were treated with cyclosporin required dialysis because their kidneys failed.[3]
Subsequent animal experiments showed that only extremely high doses of cyclosporin could induce kidney toxicity in rats,[1] although dogs and rhesus monkeys were still unaffected.[2] Researchers believe that: '...failure to produce renal dysfunction [kidney damage] experimentally that is similar to that seen clinically may result from species differences in metabolism'.[2]
Although cyclosporin can prevent the rejection of transplanted organs in both animals and human beings, an early review of the drug found sufficient variation in experimental results to indicate: 'the immunosuppressive effects of cyclosporin have...differed considerably between species, limiting any direct inference that may be made regarding use in human organ transplantation...'[1]
[1]D. J. Cohen, et al, Annals of Internal Medicine, 1984, vol. 101, pp.667-682.
[2]W. M. Bennett and J. P. Pulliam, Annals of Internal Medicine, 1983, vol. 99, pp.851-854.
[3]Lancet, 22 February 1986, pp.419-420.

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Zelmid.
In September 1987, the antidepressant zimelidine (Zelmid) was withdrawn worldwide after potentially serious side-effects, including nerve damage, leading to the loss of sensation or paralysis.[1]
Some patients experienced hypersensitivity reactions such as fever, joint pains and liver problems. The drug had been introduced only a year earlier but Britain's Committee on Safety of Medicine had received over 300 reports of adverse reactions, 60 of which were serious; there were 7 deaths.[2]
And yet prolonged testing in rats and dogs showed no evidence of toxicity even when they were given five times the human dose.[3]
[1]B. Blackwell in Side Effects of Drugs Annual, vol. 8, eds M. N. G. Dukes and J. Elis (Elsevier, 1984).
[2]R. D. Mann, Modern Drug Use; An Inquiry on Historical Principles (MTP Press, 1984).
[3]R. C. Heel, et al, Drugs, 1982, vol. 24, pp.169- 206.


CONTINUED ON PART 2

SOURCE: http://vivisection-absurd.org.uk/errors.html